ABSTRACT
OBJECTIVES: We investigated the effect of ranolazine on endothelial-dependent vasodilatation (EDV), serum markers of endothelial dysfunction, and inflammation. BACKGROUND: Endothelial dysfunction has been shown to be independently associated with the occurrence of cardiovascular events. We sought to investigate whether ranolazine, a novel antianginal medication with no effect on heart rate or blood pressure, improves endothelial function in patients with stable coronary artery disease (CAD). METHODS: Twenty-seven patients with stable CAD were randomly assigned to either 1000 mg twice daily of ranolazine or to matching placebo for 6 weeks and then crossed over for an additional 6 weeks in a double-blind design. EDV was assessed using reactive hyperemia peripheral arterial tonometry (RH-PAT) at baseline, 6, and 12 weeks. Markers of endothelial dysfunction and inflammation were also evaluated. RESULTS: After 6 weeks, treatment with ranolazine significantly increased the EDV RH-PAT index as compared with baseline (1.85+/-0.42 vs. 2.08+/-0.57, P = 0.037). EDV RH-PAT did not change while on placebo (1.69+/-0.35 vs. 1.78+/-0.41, P = 0.29). In addition, there was a significant drop in asymmetric dimethylarginine levels with ranolazine treatment (0.66+/-0.12 vs. 0.60+/-0.11 micromol/l, P = 0.02) and a near significant decrease in C-reactive protein levels (0.40+/-0.80 vs. 0.30+/-0.61 mg/dl, P = 0.05). CONCLUSION: Ranolazine improves endothelial function, asymmetric dimethylarginine, and C-reactive protein levels in a group of patients with stable CAD. Our results suggest a novel mechanism of action of ranolazine.
Subject(s)
Acetanilides/therapeutic use , Cardiovascular Agents/therapeutic use , Coronary Artery Disease/drug therapy , Endothelium, Vascular/drug effects , Piperazines/therapeutic use , Vasodilation/drug effects , Acetanilides/adverse effects , Aged , Arginine/analogs & derivatives , Arginine/blood , Biomarkers/blood , C-Reactive Protein/metabolism , Cardiovascular Agents/adverse effects , Coronary Artery Disease/blood , Coronary Artery Disease/physiopathology , Cross-Over Studies , Double-Blind Method , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Humans , Hyperemia/physiopathology , Inflammation Mediators/blood , Male , Manometry , Middle Aged , Piperazines/adverse effects , Ranolazine , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The present study was undertaken to investigate the effect of statins plus omega-3 polyunsaturated fatty acids (PUFAs) on endothelial function and lipid profile in South Asians with dyslipidemia and endothelial dysfunction, a population at high risk for premature coronary artery disease. METHODS: Thirty subjects were randomized to rosuvastatin 10 mg and omega-3-PUFAs 4 g or rosuvastatin 10 mg. After 4 weeks, omega-3-PUFAs were removed from the first group and added to subjects in the second group. All subjects underwent baseline, 4-, and 8-week assessment of endothelial function and lipid profile. RESULTS: Compared to baseline, omega-3-PUFAs plus rosuvastatin improved endothelial-dependent vasodilation (EDV: -1.42% to 11.36%, p = 0.001), and endothelial-independent vasodilation (EIV: 3.4% to 17.37%, p = 0.002). These effects were lost when omega-3-PUFAs were removed (EDV: 11.36% to 0.59%, p = 0.003). In the second group, rosuvastatin alone failed to improve both EDV and EIV compared to baseline. However, adding omega-3-PUFAs to rosuvastatin, significantly improved EDV (-0.66% to 14.73%, p = 0.001) and EIV (11.02% to 24.5%, p = 0.001). Addition of omega-3-PUFAs further improved the lipid profile (triglycerides 139 to 91 mg/dl, p = 0.006, low-density lipoprotein cholesterol 116 to 88 mg/dl, p = 0.014). CONCLUSIONS: Combined therapy with omega-3-PUFAs and rosuvastatin improves endothelial function in South Asian subjects with dyslipidemia and endothelial dysfunction.
